摘要
目的:研究右美托咪定(DEX)联合乌司他丁(UTI)对脂多糖(LPS)诱导的大鼠急性肺损伤(ALI)的影响。方法:健康雄性Wistar大鼠40只,随机分为5组:生理盐水对照组(NS组)、LPS模型组(L组)、右美托咪定治疗组(L+D组)、乌司他丁治疗组(L+U组)和右美托咪定+乌司他丁治疗组(L+D+U组)。对照组股静脉给予5 mL/kg生理盐水(NS);模型组股静脉给予LPS(10 mg/kg);右美托咪定治疗组股静脉给予LPS(10 mg/kg),即刻持续输注右美托咪定(1μg·kg-1·h-1);乌司他丁治疗组股静脉给予LPS(10 mg/kg),即刻腹腔注射乌司他丁(50 000 U/kg);右美托咪定联合乌司他丁治疗组股静脉给予LPS后立即持续输注右美托咪定(1μg·kg-1·h-1)及腹腔注射乌司他丁(50 000 U/kg)。在注射LPS或NS后6 h处死动物。血气分析检测动脉血氧分压(PaO2)、pH和碱剩余(BE);HE染色光镜下观察肺组织病理学变化并进行肺损伤评分;检测肺组织湿干重比(W/D)、髓过氧化物酶(MPO)活性、丙二醛(MDA)、肿瘤坏死因子α(TNF-α)、白细胞介素1β(IL-1β)、巨噬细胞炎症蛋白2(MIP-2)、一氧化氮(NO)及前列腺素E2(PGE2)的含量;检测支气管肺泡灌洗液(BALF)中白蛋白浓度;提取肺组织核蛋白,检测NF-κB p65的表达。结果:与NS组比较,L组动脉血PaO2、pH和BE降低,肺组织水肿、出血、炎症细胞浸润程度及肺损伤评分上升,肺组织TNF-α、IL-1β、MIP-2、MDA、NO、PGE2含量及W/D升高,MPO活性升高,肺组织NF-κB表达明显升高。与L组相比,联合治疗组动脉血PaO2、pH和BE上升,肺组织水肿、出血、炎症细胞浸润程度及肺损伤评分降低,TNF-α、IL-1β、MIP-2、MDA、NO、PGE2含量及W/D降低,MPO活性降低,肺组织NF-κB表达降低;与L组相比,右美托咪定和乌司他丁单独治疗组上述指标没有明显变化。结论:右美托咪定联合乌司他丁能够减轻脂多糖诱导的大鼠急性肺损伤。
AIM： To investigate the effects of dexmedetomidine-ulinastatin combination on acute lung injury induced by lipopolysaccharide （LPS） in rats. METHODS ： Male Wistar rats were randomly divided into 5 groups ： saline control group （NS group） was given saline （5 mL/kg, iv） alone; LPS group （L group） was given LPS （10 mg/kg, over 10 rain） ; dexmedetomidine ＋ LPS group （L ＋ D group） was treated with the additional administration of dexmedetomidine （ 1 Ixg kg- 1 . h - ~ ） immediately after LPS injection; ulinastatin ＋ LPS group （ L ＋ U group） was treated with the addi- tional administration of ulinastatin （50 000 U/kg, ip） immediately after LPS injection; dexmedetomidine ＋ ulinastatin ＋ LPS group （L＋D ＋U group） received dexmedetomidine （1 Ixg ＂ kg-l ＂ h-l） and ulinastatin （50 000 U/kg） immediately after LPS injection. The animals were sacrificed at 6 h after LPS or NS administration. Partial pressure of arterial oxygen （ Pa02 ） , pH and base excess （BE） were measured, and the lungs were removed for evaluation of histological characteris- tics and determining the concentrations of TNF-ot, IL-113, macrophage inflammatory protein 2 （ MIP-2）, malondialdehyde （MDA）, nitric oxide （ NO）, prostaglandin E2 （ PGE2 ） and myeloperoxidase （MPO） in lung tissues, lung wet/dry weight ratio （W/D）, and albumin in brochoalveolar lavage fluid （BLAF）. The pulmonary expression of nuclear factor kappa B （NF-KB） p65 was evaluated by Western blotting. RESULTS： Compared with NS group, PaO2, pH and BE was lower inL group, which was increased by treatment with dexmedetomidine-ulinastatin combination but not by dexmedetomidine or ulinastatin alone. Compared with NS group, LPS induced marked lung histological injury, which was less pronounced in the animals treated with dexmedetomidine-ulinastatin combination but not dexmedetomidine or ulinastatin alone. The levels of IL- l[3, IL-6, MIP-2, MDA, NO and PGE2 in the lung tissues increased in L group compared with NS group, which were re- duced by dexmedetomidine-ulinastatin combination but not by dexmedetomidine or ulinastatin alone. The MPO activity, MDA level and W/D increased in the lung tissues in L group compared with NS group, which was reduced by dexmedetomidine-uli- nastatin combination but not by dexmedetomidine or ulinastatin alone. Compared with NS group, the albumin concentration in the BLAF increased, which was reduced by dexmedetomidine-ulinastatin combination but not by dexmedetomidine or ulinasta- tin alone. Compared with NS group, the expression of NF-KB p65 increased in L group, which was reduced by dexmedeto- midine-ulinastatin combination but not by dexmedetomidine or ulinastatin alone. CONCLUSION： Dexmedetomidine-uli- nastatin combination has a protective effect on LPS-induced acute lung injury in the rats.
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2014年第1期96-101,共6页
Chinese Journal of Pathophysiology
